Depression

PEBC

depression

• state of low mood that can affect emotional, physical, cognitive and behavioural well-being

persistent depressive disorder

• ≥2 yrs, a person has experienced a depressed mood more days than not PLUS ≥2 of the following:

• appetite loss or overeating (changes in appetite)

• sleep disturbances

• low energy/ fatigue

• low self-esteem

• hopelessness

• poor concentration or indecisiveness

major depressive disorder

• ≥5 of the following sx for at least 2 weeks; at least 1 must be depressed mood or loss of interest/ pleasure:

• depressed mood

• markedly reduced interest or pleasure in all activities

• appetite loss or overeating

• sleep disturbances

• low energy/ fatigue

• agitation or psychomotor retardation

• feeling worthless or excessive/ inappropriate guilt

• poor concentration

• recurrent thoughts of death

medications:

• takes at least 2-4 weeks to show any effect and 6-8 weeks for Full effect

clinical presentation

SADAFACES

• Sleep changes

• Anhedonia (reduced ability to experience pleasure)

• Depressed mood

• Appetite disturbance

• Fatigue

• Agitation (psychomotor) or psychomotor retardation

• Concentration (diminished)

• Esteem (low)

• Suicidal ideation

PHQ9 scale

• self administered screening tool for depression

• MDD suggested if of the 9 items, 5+ are checked as at least “more than half the days”

  • either item 1 or 2 is checked as at least “more than half the days”

risk factors (depression)

Non-modifable:

• Females (males catch up later in life)

• Family history (1st degree)

• Hx of adverse childhood experiences, traumatic life events, death of spouse

• age 25-44

Potentially modifiable:

• Chronic medical conditions and psychiatric comorbidities (DM, CVD, Anxiety, Chronic pain)

• Alcohol and substance use disorders

• Periods of hormonal changes

• Significant life stressors

• Bereavement

• Environmental/ lifestyle factors

risk factors (suicide)

comorbid conditions:

• PTSD

• Substance use disorder (of family hx)

• Comorbid personality disorders

• Sleep disorders, chronic pain conditions

life events:

• suicidal ideation, prior attempts

• hopelessness, anxiety, impulsivity, psychosis

• significant life stressors

• increasing age, being widowed or unmarried

• unemployed or living alone

• anniversary of a loss

• ethnicity - First Nations

• Females = more prone to OD

drug induced causes

• Antipsychotics

• Anticonvulsants (levetiracetam, phenobarbital, primodine, phenytoin, tigabine, topiramate, vigabatrin)

• Corticosteroids

• Parkinsons disease drugs

• Isotretinoin

• Sex hormones (oral contraceptives, Tamoxifen, GnRH agonists)

• stimulants

  others:

• anti-virals

• Beta blockers

• calcium channel blockers

• clonidine

• interferon alpha/beta

• methyldopa

• PPIs

• H2RAs

• Reserpine

• sex hormones

• statins

• triptans

• varenicline

goals of therapy

1. attain relief from depressive sx

2. treat concurrent sx/ disorders w minimal side effects

3. restore optimal functioning and QoL

4. prevent suicide

5. prevent future episodes

non pharm

1. Psychoeducation and self-management

   • as effective as drug therapy and preferred over meds

   • moderate MDD = choice btwn meds and/or psychotherapy

   • severe MDD = combo of meds and psychotherapy

   • most evidence = CBT, IPT and BA

   • psychotherapy combined with pharmacotherapy = more effective than either alone

2. Regular exercise (aerobic and resistance)

   • proven to prevent and treat depression (low intensity 30-40 mins 3-4x weekly min 9 weeks)

   • 1st line monotherapy in mild depression

   • 2nd line adjunct in moderate depression

3. ECT (electroconvulsive therapy)

   • 1st line in severe and life threatening situations

4. Light therapy

   • 1st line monotherapy in seasonal pattern MDD - improve in 1-3 weeks

   • 2nd line for mild depression non-seasonal

algorithm

treatment options

follow up within 2 weeks of starting anti-depressant

duration of therapy

• acute phase (8-16 weeks until sx remission)

  • address pt safety

  • treat to sx remission and functional improvement

  • prevent suicide

  • overall = resolution of sx

• maintenance (6-24 months) or longer

  • maintain remission

  • restore functioning

  • prevent recurrence

  • DC treatment when clinically indicated

• all pts should be treated for 6-12 months after remission

• treatment should be continued for ≥2 yrs if ANY of following RF for recurrence are present:

  • persistent residual sx (anhedonia, sleep problems, cognitive dysfunction)

  • Hx of childhood abuse

  • increased severity of depressive sx

  • chronic depressive episodes

  • psychiatric or non-psychiatric comorbidities

  • increase number of previous episodes (3+)

  • poor social support

  • persistent life events

8-16 weeks

duration of therapy for the acute phase

• address patient safety

• treat symptom remission and functional improvement

• prevent suicide

6-24 months

duration of therapy for the Maintenance phase!

• can be longer if clinically indicated

• maintain symptomatic remission

• restore functioning

• prevent recurrence

• discontinue treatment when clinically indicated

6-12 months

duration of therapy after remission

2+ years

duration of treatment when any of the following risk factors for recurrence are present:

• persistent residual symptoms (anhedonia, sleep problems, cognitive dysfunction)

• history of childhood abuse

• increased severity of depressive episodes

• chronic depressive episodes

• psychiatric or nonpsychiatric comorbidities

• increased # of previous episodes (3+ episodes)

• poor social support

• persistent life events

SSRI

Escitalopram, Citalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline

• time to onset = 2-4 weeks

• start low and titrate up gradually

• fluoxetine = drug of choice in CHILDREN

  • lots of nausea

  • fluoxi-teen = for teens and kids

• Combining with NSAIDs = increased GI Bleed risk

• combining with diuretics = hyponatremia (esp in elderly)

• most anticholinergic = Paroxetine

  • weight gain with paroxetine

• s/e = HA, dizziness, anxiety/agitation (esp in first 1-2 weeks), Nausea, sleep disturbance, Sexual dysfunction

• escitalopram and citalopram = QTc prolonging

• Concurrent use with MAOIs, linezolid and methylene blue is contraindicated due to increased risk of serotonin syndrome.

SNRI

Venlafaxine, Desvenlafaxine, Duloxetine, Levomilnacipran

• time to onset = 2-4 weeks

• Duloxetine = benefits for comorbid pain; associated with drug induced liver injury

• Desvenlafaxine = low incidence sexual dysfunction

• s/e = tremor, agitation, sweating, palpitations, nausea, HA, insomnia, sexual dysfunction, hyponatremia, anticholinergic

• Venlafaxine = Dose-related hypertension occurs rarely, particularly at doses ≥225 mg/day

Bupropion

• Low incidence of sexual dysfunction!!! use this is pt is experiencing sexual dysfunction from other options

• no weight gain

• may increase anxiety

• s/e = stimulating: agitation, insomnia, tremor, increase HR/BP, decrease appetite, decrease weight

• lowers seizure threshold

• C/I= Sz disorders, recent Hx of anorexia or bullimia

• alcohol use can also lower Sz threshold

• drug induced liver injury

• caution: crcl <30, hepatic impairment

mirtazapine

• high rate of drowsiness and weight gain, increase appetite and long term metabolic risks

• low incidence of sexual dysfucntion

• s/e = dry mouth, wt gain, increased appetite, drowsiness, edema, arthralgia, dizziness

trazodone

• very sedating! and rarely tolerated at therapeutic doses

• used as a sedative

• no tolerance

• s/e = sedation, decreased BP, dizziness, HA, priapism, increased QTc

vortioxetine

• low incidence of sexual dysfunction

• s/e = well tolerated, nausea, decreased sexual dysfunction

• long half life

TCAs

Amitriptyline, Nortriptyline, Clomipramine, Desipramine, Impiramine, doxepin

• 2nd line

• time to onset = 2-4 weeks

• LOTS OF SE = sedation, decreased BP, dizziness, sexual dysfunction, sweating, tremor, anticholinergic, increased wt,

  • increased HR, QTc, ECG changes

• AVOID in pts with hx of overdose due to risk of cardiotoxicity, altered mental status and seizures

MAOIs

Phenelzine, Tranylcypromine, Moclobemide (use this and avoid the others)

• associated with potentially fatal food interactions: hypertensive crisis when using tyramine rich food = cured meats, mature cheese, fermented products (miso, kimchi)

• interactions = dextromethorphan, SSRIs, St johns wort

• s/e = dry mouth, insomnia, HA, nausea, decreased sexual dysfunction

• highest risk of serotonin syndrome with irreversible MAOIs = Phenelzine and Tranylcypromine

SSRI side effects

SNRI side effects

TCA side effects

overview of side effects

side effect management

serotonin syndrome

SHIVERS

• Shivering

• Hyperreflexia

• Increased temperature

• Vital signs unstable (Increased HR, RR, Low BP)

• Encephalopathy (confused, altered mental status)

• Restlessness

• Sweating

when theres too much serotonin in body

• when multiple serotonergic agents used concomitantly

• AVOID when using other serotonergic agents:

  • linezolid, MAOIs, dye methylene blue

• DC offending agents immediately! go to ER

switching antidepressants

• direct switch = stop 1st agent abruptly and start new antidepressant next day

• Taper and switch immediately = gradually taper 1st agent and then start the new agent immediately after discontinuation ←- best way

• taper and switch after washout = gradually withdraw 1st, then start new after washout period (depends on half life of 1st drug)

• cross taper = taper the first (over 1-2 weeks or longer) and build up the dose of the new agent simultaneously

withdrawal/ discontinuation syndrome

• rapid or abrupt d/c or dose reduction of most antidepressants may be associated with discontinuation syndrome —> esp if taken 6 weeks or more

FINISH

Flu-like sx

Insomnia

Nausea

Imbalance

Sensory changes

Hyperarousal

• usually lasts 3 days - 3 weeks

• can be prevented by counselling patients to not stop drug abruptly

• resolve w/in 48 hr if SSRI/SNRI re-introduced

• highest risk = paroxetine and venlafaxine bc they have short t1/2

• bupropion doesnt cause withdrawal

• fluoxetine = lowest incidence of withdrawal due to long half-life

pregnancy and breastfeeding

• psychotherapy = 1st line

• pharmacotherapy given if:

  • severe sx

  • high risk of relapse

  • unable to access or have inadequate response to psychotherapy

  • prefer to use meds

• 1st line:

  • citalopram, escitalopram, sertraline

• 2nd line:

  • bupropion, desvenlafaxine, venlafaxine, fluoxetine, fluvoxaine, duloxetine, mirtazapine

• 3rd line:

  • TCA, trazadone, Quetiapine

• avoid paroxetine in pregnancy = cardiovascular malformations

• AVOID DOXEPIN in breastfeeding = sedation in infant

st johns wort

• mild depression = 1st line

• moderate depression = 2nd line

• potent inducer of CYP3A4 and P-gp = decrease bioavailability of many drugs

acupuncture

• mild depression = 2nd line monotherapy

• moderate - severe = 2nd line adjunct

monitoring